When Cryptococcus is manifested as Cryptococcal meningitis (CM), it creates a large burden of mortality and morbidity to the patient and is very difficult for the clinician to treat. There are now 10,000 US cases and over 1 million cases of CM worldwide annually, with estimated deaths of 700,000 per year. CM is caused when Cryptococcus neoformans, a basidiomycete fungal pathogen, invades the central nervous system (CNS), It is seen most commonly in immunocompromised patients, such as those with HIV or post organ-transplant. Current treatments include anti-fungal agents that have limited effectiveness in penetrating the CNS and various systemic side effects. Reduction in pathogen burden within the first 14 days of therapy is the best predictor of reduced morbidity and mortality. Minnetronix, a medical device development and manufacturing company, proposes this Phase I STTR in collaboration with experts from the Infectious Diseases and Neurosurgery Departments at Duke University. Phase I will focus on developing Neurapheresis, a cerebrospinal fluid (CSF) processing platform, that will rapidly clear specific pathogens for treating life-threatening infections of the central nervous system (CNS). The objective of the proposed project is to develop a tailored system to target and remove C. neoformans from the CSF and to evaluate its reduction in a CM animal model. Specific Aim 1 will focus on conducting in vitro testing using a design matrix tailored for Cryptococcus exclusion. Longevity and mechanical testing will be performed to ensure safety and reliability. Specific Aim 2 will evaluate the in vivo reduction of CSF fungal CFUs in a validated rabbit CM model. In summary, Neurapheresis is an innovative, new therapeutic option that provides direct access to the CSF and creates active circulation combined with targeted pathogen removal. This treatment is intended to be complementary and does not replace standard of care (SOC) interventions with systemic, intravenous antifungal regimens. Successful completion of this Phase I STTR will provide Minnetronix with the data to justify broader preclinical studies and development of a GLP-quality system for treatment of CM in Phase II. During Phase II, concurrent regulatory, clinical planning, and reimbursement work will be conducted to prepare for an investigational device exemption (IDE) application at the end of Phase II. The long-term goal of the project is to develop a novel therapeutic approach that rapidly reduces CSF fungal burden and translates to reduced morbidity and mortality for CM patients worldwide.